Table Of Contents Page, PNAS Volume 123, Number 17
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Perspective
Evolvable AI (eAI), i.e., AI systems whose components, learning rules, and deployment
conditions can themselves undergo Darwinian evolution, may soon emerge from current
trends in generative, agentic, and embodied AI. We argue that this possibility has
...
Letters
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The cost of thinking is similar between large reasoning models and humans
This article has a reply:Reply to Hu: Reasoning traces need not be faithful to account for the cost of human thinking
Brief Reports
The demand for thermal management of electronics is rapidly increasing due to the
prosperity of information technology. However, the two major alternatives, convective
cooling and vapor compression technologies, have limitations for the effective ...
The recently emergent fungal pathogen Candidozyma (Candida) auris has produced numerous outbreaks of invasive disease in hospitals worldwide. It is
the first fungal pathogen categorized as a global public health threat due to its
ability to readily ...
This study offers a systematic analysis of scientific papers cited in both Republican
and Democratic policy documents. Using data from Overton and Dimensions, we examine
congressional reports, hearings, and think tank publications. We find that bipartisan
...
Physical Sciences
Applied Mathematics
Knots, links, and entangled filaments appear in many physical systems in biology and
engineering and their structural complexity is related to their function. In the context
of emerging AI capabilities in predicting new physical structures, as well as in ...
Herein, we present crystal structures of proteins adopting a fold not identified among
known
Applied Physical Sciences
Ferroelectric nematic liquid crystals (FNLCs) represent an emerging class of functional
soft materials that combine the orientational order of nematic liquid crystals with
spontaneous electrical polarization. In a striking departure from the conventional
...
Biophysics and Computational Biology
Biological systems, with many interacting components, face high-dimensional environmental
fluctuations, ranging from diverse nutrient deprivations to toxins, drugs, and physical
stresses. Yet, many biological control mechanisms are “simple,” i.e., ...
Cytotoxic T lymphocytes eliminate infected or malignant cells, safeguarding surrounding
tissues. Although experimental and systems-immunology studies have cataloged many
molecular and cellular actors involved in an immune response, the design principles
...
Collective cell dynamics are fundamental to numerous physiological processes, including
embryo development, tissue morphogenesis, immune response, and disease progression.
Accurately modeling these dynamics across scales remains challenging, as ...
Chemistry
Molecular polaritons, formed by coupling molecular excitons with cavity photons, offer
a promising platform for exploring quantum phenomena. A key challenge is understanding
how these hybrid states maintain coherence in the presence of environmental ...
Collagen mineralization is fundamental to the structure and mechanical properties
of bone. Many in vitro models of collagen mineralization have been developed to understand
the regulation, from the structure of collagen fibrils to the matrix ...
Computer Sciences
Intergovernmental organizations (IGOs) attempt to shape global policy through scientific
guidelines and assessments. While they rely on external scientists to bridge research
and IGO advisory processes, the structural pathways connecting science to IGO ...
Earth, Atmospheric, and Planetary Sciences
Many petrological, geodynamical, and geochemical perspectives have offered circumstantial
evidence for either an early onset of plate tectonics in the first 10% of Earth’s
history or a late onset after the great oxidation event (2.5 Ga ago). This calls ...
Cold-region ecosystems are highly sensitive to climate change, yet the geochemical
processes shaping their future remain poorly understood. Here, we show that ice systematically
enhances mineral dissolution through freeze concentration into microscale ...
Earth’s lower mantle is dominated by (Mg,Fe)SiO3 bridgmanite. It was reported that (Mg,Fe)SiO3 decomposes into an Fe-depleted bridgmanite phase and an iron-rich phase with a hexagonal
structure (H-phase) under high pressure–temperature conditions of the ...
Engineering
Natural filaments, such as proteins, plant tendrils, octopus tentacles, and elephant
trunks, can transform into arbitrary three-dimensional shapes that carry out vital
functions. Their shape-morphing behavior arises from intricate patterning of active
and ...
Photosynthetic biomanufacturing offers a sustainable route to generate valuable bioproducts
by harnessing microorganisms such as algae to convert sunlight and carbon dioxide
into biomass. A major barrier to efficient production is that light penetrates ...
The merging of two droplets represents an energy-minimizing process whereby they combine
to produce a thermodynamically stable droplet. Coalescence of Newtonian droplets is
characterized by distinct viscous and inertial regimes. In contrast, viscoelastic
...
A long-standing engineering problem, the control of soft robots is difficult because
of their highly nonlinear, heterogeneous, anisotropic, and distributed nature. Here,
bridging engineering and biology, neural reservoirs are employed for the dynamic ...
Many fundamental biological processes—spanning immune–tumor interactions, neuronal
signaling, and microvascular flow—exhibit fast, multiscale dynamics among diverse
cell types within three-dimensional tissue environments. Capturing such activity requires
...
Simultaneous interrogation of cardiac electrophysiological and metabolic processes
is essential for investigating and treating heart disease. Key challenges remain in
creating stretchable multimodal bioelectronic devices capable of organ-scale, label-free
...
Mobile robots are increasingly deployed in diverse settings, ranging from logistic
and household applications to ecological monitoring and operation in extreme environments.
In these contexts, robots must traverse diverse terrains, yet most existing ...
Measuring fast dynamic processes with dynamic light scattering over wide fields of
view is critical for applications ranging from blood flow imaging to characterizing
complex fluids, yet is often limited by the need for expensive, high frame rate cameras.
...
Statistics
We establish network predictability theory by mapping link prediction onto a spin
glass model, where network partitions correspond to spin configurations, and predictability
equals the system’s average energy. Using the cavity method from statistical ...
Social Sciences
Demography
Reproductive-age populations show a growing male surplus around the globe as a consequence
of declining mortality, narrowing sex differences in mortality, and sex-selective
abortions in some countries. Population structures are important determinants of ...
Women in different-sex couples experience larger economic losses after separation
than men, largely due to unequal divisions of paid and unpaid work. Women in female
same-sex couples divide paid and unpaid work more equally, offering a unique opportunity
...
Psychological and Cognitive Sciences
Embodied accounts of morality propose that corporeal self-awareness helps restrain
immoral actions. The Sense of Agency (SoA)—the feeling of controlling one’s actions
and their consequences—drops when individuals harm others. However, whether modulating
...
Everyday tasks, such as selecting routes when driving or preparing meals, require
making sequences of embodied decisions, in which planning and action processes are
intertwined. Here, we address how people make sequential embodied decisions, requiring
...
Human curiosity is dynamic, however the principles governing its fluctuations remain
debated. Here, we test two competing hypotheses about how past learning shapes subsequent
curiosity and memory. The first, based on the “optimal arousal” theory, proposes ...
Human visual perception for basic dimensions varies with eccentricity and polar angle,
influencing daily activities such as reading, searching, and scene perception. We
investigated whether and how system-level computations that transform visual input
...
Social Sciences
A persistent puzzle throughout the cognitive and social sciences is how people manage
to learn social conventions from the sparse and noisy behavioral data of diverse actors,
without explicit instruction. Here, we show that the dominant theories of social ...
Communities reliant on extractive industries face a paradox: Despite the promise of
economic growth from lucrative, well-paying industries, they often experience poor
socioeconomic outcomes. While the so-called “resource curse” has been debated and
...
For more than a century, studies have shown that children who grow up in homes with
more books achieve higher levels of academic success, yet it remains unclear whether
books themselves improve learning or simply reflect broader socioeconomic advantages.
...
Sustainability Science
Intergovernmental organizations (IGOs) attempt to shape global policy through scientific
guidelines and assessments. While they rely on external scientists to bridge research
and IGO advisory processes, the structural pathways connecting science to IGO ...
Biological Sciences
Agricultural Sciences
Rice production underpins food security but relies heavily on nitrogen (N) fertilization,
much of which is lost as gaseous emissions. Dinitrogen (N2) represents the largest N loss, yet its sources remain poorly constrained because
biological dinitrogen (N...
As a staple food for half the world’s population, rice is an important dietary source
of magnesium (Mg), an essential mineral for human health. Enhanced Mg accumulation
in rice grains has also been linked to eating quality. However, the mechanisms ...
Anthropology
The Middle Awash study area of Ethiopia’s Afar Rift features a composite stratigraphic
thickness of >1 km. Near the top of this succession lie sediments of the lower Halibee
member, comprising the Faro Daba and Chai Baro beds. The former are ...
This paper examines human life history evolution across the transition to agriculture
in Europe through an integrated analysis of growth, diet, activity, and demography.
Life history theory considers how organisms allocate energy toward defense, ...
Applied Biological Sciences
Limb loss remains a significant clinical challenge, but regenerative medicine approaches
such as gene therapy offer a promising strategy to trigger endogenous regeneration
programs. Optimal vector configurations and molecular targets for appendicular ...
Biochemistry
Collagen mineralization is fundamental to the structure and mechanical properties
of bone. Many in vitro models of collagen mineralization have been developed to understand
the regulation, from the structure of collagen fibrils to the matrix ...
MutS and MutL proteins and their eukaryotic homologs have important functions in DNA
metabolism. MutLβ (MLH1-PMS1 heterodimer) is a poorly understood eukaryotic MutL complex.
Recent genetic studies have implicated MutLβ in the process of expansion of the ...
Nerve growth factor (NGF) is a member of the neurotrophin family, essential for neuronal
survival and phenotypic maintenance. However, in vitro, its function can be disrupted
by oxidative posttranslational modifications such as tyrosine nitration. ...
Biophysics and Computational Biology
Cytotoxic T lymphocytes eliminate infected or malignant cells, safeguarding surrounding
tissues. Although experimental and systems-immunology studies have cataloged many
molecular and cellular actors involved in an immune response, the design principles
...
Herein, we present crystal structures of proteins adopting a fold not identified among
known
NMR spectroscopy is ubiquitous in many areas of science, including chemistry, material
science, biophysics, and structural biology. Heteronuclear two-dimensional (2D) NMR
experiments form the basis of several NMR-based investigations, especially those ...
The aggregation of amyloid proteins into fibrillar and oligomeric aggregates is linked
to a number of neurodegenerative diseases. While the disease onset remains elusive
in many cases, an understanding of the driving forces for the aggregation may help
...
Cell Biology
Chromosomal instability (CIN) is a prevalent form of genomic instability in prostate
cancer (PCa). However, its molecular mechanisms remain inadequately understood. This
study demonstrates that reduced expression of UFM1-ligase 1 (UFL1) is commonly ...
The mitotic kinase Aurora-A is frequently overexpressed in cancers and contributes
to tumor progression and therapy resistance, yet the mechanisms underlying its role
in drug resistance remain unclear. Here, we show that sorafenib treatment triggers
...
In the zebrafish retina, Müller glia (MG) respond to retinal injury by dividing and
producing a multipotent progenitor for retinal repair. This cell division is regulated
by microglia; however, the underlying mechanism remains unknown. Here, we report ...
In the process of investigating innate immune reactions against injected oncogenic
cells in Drosophila, we noted that the homeodomain protein Engrailed, known since last century for its
role in segmentation polarity in embryos, is reactivated in adult ...
Developmental Biology
Throughout the central nervous system, the fate and migration of projection neurons
(PNs) are tightly coordinated to ensure that specific neuronal fates settle in precise
spatial locations. This is particularly evident in the mammalian neocortex, where
...
Adhesion G protein–coupled receptors (AGPCRs) regulate essential physiological processes
through interactions between their ectodomains and adjacent cell surface proteins
or extracellular matrix components (ECM). AGPCRs distinctively arrive at the plasma
...
Ecology
Atlantic bluefin tuna (ABT) are a highly migratory fish that have been exploited by
fishers for more than two millennia. This lucrative fishery is managed by the International
Commission for Conservation of Atlantic Tunas (ICCAT), formed by 55 contracting ...
Whether bigger brains provide enhanced cognitive capacities is a long-lasting and
controversial question. While big brains may not be required for producing sophisticated
behavior, they could facilitate information processing and memory storage. Here, we
...
Disruption of habitat connectivity alters host movement patterns and pathogen exposure
in wildlife. Changes in exposure dynamics have led to increased research interest
in host-associated microbial communities (i.e., microbiomes), particularly in how
...
Climate change induced extreme weather events (EWEs) and invasive species are major
threats to global biodiversity and social economy; however, the unique role of EWEs
in facilitating biological invasions remains uncertain. Here, we compiled an extensive
...
Evolution
Biological systems, with many interacting components, face high-dimensional environmental
fluctuations, ranging from diverse nutrient deprivations to toxins, drugs, and physical
stresses. Yet, many biological control mechanisms are “simple,” i.e., ...
The extent to which human adaptations have persisted throughout history despite strong
eroding demographic events such as admixture, genetic drift, and fluctuations in selection
pressures remains unknown. Understanding which adaptations were resilient to ...
The future of tropical forests depends on their ability to resist and recover from
multiple disturbances. Here, we evaluated how edge effects, experimental fires, extreme
droughts, and blowdowns reshaped forest structure, composition, and functional ...
The evolution of genetic sex determination (GSD) from environmental sex determination
(ESD) remains a fundamental issue in evolutionary biology. However, the mechanisms
driving the transition, particularly in its earliest stages, are largely unknown.
Here,...
Natural variation in metabolism is a key driver of microbial adaptation. While galactose
utilization is well studied in budding yeasts, it remains poorly understood in the
fission yeast Schizosaccharomyces pombe. Here, we reveal extensive natural ...
Stop codon readthrough is widespread across eukaryotes and often dismissed as translational
noise, yet its tissue/stage-specific occurrence suggests adaptive roles in proteome
tuning. We asked whether readthrough-related mechanisms can mitigate stage-...
Genetics
Cohesin is a conserved protein complex that mediates sister chromatid cohesion, chromosome
condensation, gene regulation, and DNA repair. These processes rely on cohesin’s ability
to tether DNA and form chromatin loops, which depend on cohesin’s ATP ...
Immunology and Inflammation
Autoimmune nodopathies (AINs) are rare acquired autoimmune neuropathies with distinct
clinical features and circulating autoantibodies, often of the immunoglobulin G4 (IgG4)
subclass, targeting proteins at the node of Ranvier. Defects in B cell tolerance ...
Medical Sciences
Polyene antifungals (PAs) have long constituted an irreplaceable lifesaving treatment
for lethal fungal infections. However, PAs induce significant dose-dependent nephrotoxicity,
primarily because of their binding to cholesterol in the renal cell membrane,...
Non–small cell lung cancer (NSCLC) patients with tumors harboring STK11 mutations are resistant to standard of care anti-PD-1/PD-L1 blockade. For this patient
population there are no currently available tailored treatments, underlying the critical
need to ...
Adoptive T cell therapies typically rely on ex vivo CD3/CD28 stimulation, which promotes
effector differentiation and limits the persistence of transferred cells. Stem cell–like
memory T cells (Tscm), with their capacity for self-renewal and multipotency, ...
Microbiology
Bacteriophages target membrane-anchored glycopolymers to promote host cell lysis and progeny release
Most bacteriophages lyse their host cell to release progeny virions. Double-stranded
DNA phages typically promote host lysis using a holin-endolysin system. Holins form
pores in the cytoplasmic membrane allowing endolysins access to the peptidoglycan
(PG) ...
Gut microbial community composition varies from one person to another. Potentially,
this means the ecological interactions experienced by individual strains or species
also vary among microbiomes of different people. However, testing this directly in
...
Influenza D virus (IDV), primarily found in livestock species, has demonstrated cross-species
transmission potential, yet its threat to humans remains poorly understood. Here,
we curated a panel of IDV isolates collected during field surveillance from ...
Microbial interactions, particularly bacteria–fungus interactions, are research hotspots
within microbial ecology and pathogenic biology. However, their underlying molecular
mechanisms remain poorly understood, especially how bacterial pathogens recognize
...
Sialic acids (Sia) on glycoproteins and glycosphingolipids act as receptors for many
respiratory viruses, including human influenza A viruses and respiroviruses, which
typically bind to α2-6- and α2-3-linked Sia (2-6Sia and 2-3Sia), respectively. In
view ...
Daptomycin is a last resort antibiotic used to treat vancomycin-resistant enterococcal
infections, but daptomycin resistance (DAPR) arises quickly during treatment. Resistance is due to sequential acquisition of
point mutations in the two-component system ...
Broad-spectrum antibiotics are frequently administered to intensive care unit patients
as part of empiric care. This treatment has been associated with subsequent infections
by the emerging nosocomial pathogen Acinetobacter baumannii; however, the ...
Chronic hepatitis B virus (HBV) infection affects nearly 300 million people worldwide.
Progress in understanding HBV immunopathogenesis and developing curative therapies
has been hindered by the lack of suitable small animal models. HBV exhibits strict
...
Neuroscience
Measuring fast dynamic processes with dynamic light scattering over wide fields of
view is critical for applications ranging from blood flow imaging to characterizing
complex fluids, yet is often limited by the need for expensive, high frame rate cameras.
...
Human curiosity is dynamic, however the principles governing its fluctuations remain
debated. Here, we test two competing hypotheses about how past learning shapes subsequent
curiosity and memory. The first, based on the “optimal arousal” theory, proposes ...
Although dysregulated serotonergic neurotransmission has been implicated in the pathophysiology
of tinnitus, the precise neural circuit mechanisms underlying this complex sensory
neurological disorder remain elusive. In the current study, we investigated ...
Changes to speech offer a quantifiable means to assess speech motor learning, and
the resulting memory is thought to be motor in nature. Here, we evaluate this idea
and show instead that memory for speech movements has a sensory basis. Speech motor
...
The presence of neuromelanin is a characteristic feature of the human substantia nigra
(SN); however, the mechanism of its synthesis and its role in the development of Parkinson’s
disease remain unclear. Here, we report that the host defense enzyme ...
Focal cortical dysplasia (FCD) is a major cause of drug-resistant epilepsy and displays
substantial clinical and histopathological heterogeneity, yet the cellular and molecular
bases underlying this diversity remain poorly defined. Here, we performed ...
Synaptic strength is dynamically modulated not only by activity-dependent processes
but also by neuromodulators. These modulators can enhance or depress synaptic transmission
and play essential roles in circuit function and in the pathophysiology of ...
Polyadic synapses (where each active zone is juxtaposed with multiple postsynaptic
targets) are found in many brain regions and are implicated in learning and memory,
yet little is known about how they function. To address this question, we analyze
...
Physiology
Sterols, lipids, and carotenoids are major metabolites that share common biosynthetic
precursors and underpin key physiological processes in eukaryotes. Yet, how cells
coordinate metabolic flux through these competing pathways to maintain homeostasis
...
Plant Biology
Many plants, unlike most animals, can reproduce as clones [D. Kester, HortScience 18, 831–837 (1983), 10.21273/hortsci.18.6.831]. Cloning plants is vital to agriculture
and biotechnology [H. Barton, T. Denham, Quatern. Int. 489, 17–25 (2018), O. L. ...
Mitochondrial dynamics—continuous fission and fusion—are hallmarks of these organelles
and essential for mitochondrial function across eukaryotes. While fission is relatively
well understood in plants, the mechanism of fusion remains incompletely defined. ...
Population Biology
The resurgence of measles in the United States, driven by declining childhood vaccination
coverage, poses a substantial public health and economic threat. Using county-level
Measles–Mumps–Rubella (MMR) vaccine coverage data and spatial incidence models, ...
Psychological and Cognitive Sciences
Embodied accounts of morality propose that corporeal self-awareness helps restrain
immoral actions. The Sense of Agency (SoA)—the feeling of controlling one’s actions
and their consequences—drops when individuals harm others. However, whether modulating
...
Human visual perception for basic dimensions varies with eccentricity and polar angle,
influencing daily activities such as reading, searching, and scene perception. We
investigated whether and how system-level computations that transform visual input
...
Cover image: Pictured is japonica rice at the milk grain stage in southern China. Yuanyuan Lei, Zhijun Wei et al. simultaneously measured dinitrogen, ammonia, and nitrous oxide emissions to explore the sources of gaseous nitrogen losses from flooded rice fields. Rather than primarily originating from nitrogen fertilizer as previously thought, 72–75% of dinitrogen emissions arose from soil organic nitrogen that was mobilized through a microbially driven nitrogen pump fueled by the fertilizer. The results could inform management strategies to enhance both the productivity and environmental sustainability of rice. See the article by Lei, Wei et al. e2603983123. Image credit: Longlong Xia.
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